Purinergic Signalling最新文献

{"title":"Gene regulation in activated microglia by adenosine A₃ receptor agonists: a transcriptomics study.","authors":"Alejandro Lillo, Joan Serrano-Marín, Jaume Lillo, Iu Raïch, Gemma Navarro, Rafael Franco","doi":"10.1007/s11302-022-09916-9","DOIUrl":"10.1007/s11302-022-09916-9","url":null,"abstract":"<p><p>Most neurodegenerative disorders, including the two most common, Alzheimer's disease (AD) and Parkinson's disease (AD), course with activation of microglia, the resident innate immune cells of the central nervous system. A₃ adenosine receptor (A₃R) agonists have been proposed to be neuroprotective by regulating the phenotype of activated microglia. RNAseq was performed using samples isolated from lipopolysaccharide/interferon-γ activated microglia treated with 2-Cl-IB-MECA, a selective A₃R agonist. The results showed that the number of negatively regulated genes in the presence of 2-Cl-IB-MECA was greater than the number of positively regulated genes. Gene ontology enrichment analysis showed regulation of genes participating in several cell processes, including those involved in immune-related events. Analysis of known and predicted protein-protein interactions showed that Smad3 and Sp1 are transcription factors whose genes are regulated by A₃R activation. Under the conditions of cell activation and agonist treatment regimen, 2-Cl-IB-MECA did not lead to any tendency to favor the expression of genes related to neuroprotective microglia (M2).</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"237-245"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10678114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X7 receptors and pannexin1 hemichannels shape presynaptic transmission.","authors":"Nathalia Vitureira, Alberto Rafael, Verónica Abudara","doi":"10.1007/s11302-023-09965-8","DOIUrl":"10.1007/s11302-023-09965-8","url":null,"abstract":"<p><p>Over the last decades, since the discovery of ATP as a transmitter, accumulating evidence has been reported about the role of this nucleotide and purinergic receptors, in particular P2X7 receptors, in the modulation of synaptic strength and plasticity. Purinergic signaling has emerged as a crucial player in orchestrating the molecular interaction between the components of the tripartite synapse, and much progress has been made in how this neuron-glia interaction impacts neuronal physiology under basal and pathological conditions. On the other hand, pannexin1 hemichannels, which are functionally linked to P2X7 receptors, have appeared more recently as important modulators of excitatory synaptic function and plasticity under diverse contexts. In this review, we will discuss the contribution of ATP, P2X7 receptors, and pannexin hemichannels to the modulation of presynaptic strength and its impact on motor function, sensory processing, synaptic plasticity, and neuroglial communication, with special focus on the P2X7 receptor/pannexin hemichannel interplay. We also address major hypotheses about the role of this interaction in physiological and pathological circumstances.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"223-236"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10242813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical exercise as a modulator of the purinergic system in the control of sarcopenia in individuals with chronic kidney disease on hemodialysis.","authors":"Débora Tavares de Resende E Silva, Matheus Ribeiro Bizuti, Natan Rodrigues de Oliveira, Lucas Zannini Medeiros Lima, Victória Galletti Dos Santos Arraes, Ana Carolina Gonçalves Zietz, Carolina Zin, Guilherme Vinício de Sousa Silva, Josiano Guilherme Puhle, Fabiana Brum Haag","doi":"10.1007/s11302-023-09950-1","DOIUrl":"10.1007/s11302-023-09950-1","url":null,"abstract":"<p><p>The word sarcopenia derives from the Greek terms \"sarx\" for meat and \"penia\" for loss, thus being used to define reductions in muscle mass, muscle strength, and lower physical performance that compromise, mainly, the elderly population. Its high negative impact on patients' quality of life encourages the production and publication of new studies that seek to find methods to prevent and reverse cases of loss of muscle mass and strength. Furthermore, the high prevalence of sarcopenia in patients with chronic kidney disease (CKD) is closely related to its pathophysiology, which consists of a state of increased protein catabolism and decreased muscle tissue synthesis. Also considering the inflammatory nature of CKD and sarcopenia, the purinergic system has been an important target of studies, which seek to relate it to the two previous conditions. This system achieves anti-inflammatory action by inhibiting, through adenosine, pro-inflammatory factors such as interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-α), and nitric oxide (NO), as well as by releasing anti-inflammatory substances such as interleukin-10 (IL-10). Simultaneously, the purinergic system presents pro-inflammatory activity, signaled by adenosine triphosphate (ATP), which occurs through the activation of T cells and the release of pro-inflammatory factors such as those mentioned above. Therefore, the ability of this system to act on inflammatory processes can promote positive and negative changes in the clinical aspect of patients with CKD and/or sarcopenia. Furthermore, it appears that there is a correlation between the practice of repeated physical exercise with the clinical improvement and in the quality of life of these patients, presenting a decrease in the levels of C-reactive protein (CRP), NTPDase, and the pro-inflammatory cytokine IL-6, such as increases in IL-10 resulting from modulation of the purinergic system. In this way, the present article seeks to evaluate the effect of physical exercise as a modulator of the purinergic system in the control of sarcopenia in patients with CKD on hemodialysis, in order to trace a relationship that can bring benefits both for biological markers and for quality of life of these patients.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"213-222"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10045921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifiability of enzyme kinetic parameters in substrate competition: a case study of CD39/NTPDase1.","authors":"Anna N McGuinness, Aman Tahir, Nadia R Sutton, Andrew D Marquis","doi":"10.1007/s11302-023-09942-1","DOIUrl":"10.1007/s11302-023-09942-1","url":null,"abstract":"<p><p>CD39 (NTPDase1-nucleoside triphosphate diphosphohydrolase 1) is a membrane-tethered ectonucleotidase that hydrolyzes extracellular ATP to ADP and ADP to AMP. This enzyme is expressed in a variety of cell types and tissues and has broadly been recognized within vascular tissue to have a protective role in converting \"danger\" ligands (ATP) into neutral ligands (AMP). In this study, we investigate the enzyme kinetics of CD39 using a Michaelis-Menten modeling framework. We show how the unique situation of having a reaction product also serving as a substrate (ADP) complicates the determination of the governing kinetic parameters. Model simulations using values for the kinetic parameters reported in the literature do not align with corresponding time-series data. This dissonance is explained by CD39 kinetic parameters previously being determined by graphical/linearization methods, which have been shown to distort the underlying error structure and lead to inaccurate parameter estimates. Modern methods of estimating these kinetic parameters using nonlinear least squares are still challenging due to unidentifiable parameter interactions. We propose a workflow to accurately determine these parameters by isolating the ADPase and ATPase reactions and estimating the respective ADPase parameters and ATPase parameters with independent data sets. Theoretically, this ensures all kinetic parameters are identifiable and reliable for future prospective model simulations involving CD39. These kinds of mathematical models can be used to understand how circulating purinergic nucleotides affect disease etiology and potentially inform the development of corresponding therapies.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"257-271"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine A2A receptor-bearing GABAergic neurons in the lateral septum of the brain: novel mediators of depressive-like behavior.","authors":"Ya-Fei Zhao, Peter Illes","doi":"10.1007/s11302-023-09946-x","DOIUrl":"10.1007/s11302-023-09946-x","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"209-211"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9600657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: P2 purinergic receptors regulate the progression of colorectal cancer.","authors":"Wen-Jun Zhang, Li-Peng Zhang, Si-Jian Lin, Cheng-Yi Wang, Yi-Guan Le","doi":"10.1007/s11302-024-09995-w","DOIUrl":"10.1007/s11302-024-09995-w","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"311"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feedback facilitation by adenosine A_2A receptors of ATP release from mouse hippocampal nerve terminals.","authors":"Francisco Q Gonçalves, Pedro Valada, Marco Matos, Rodrigo A Cunha, Angelo R Tomé","doi":"10.1007/s11302-023-09937-y","DOIUrl":"10.1007/s11302-023-09937-y","url":null,"abstract":"<p><p>The adenosine modulation system is mostly composed by inhibitory A₁ receptors (A₁R) and the less abundant facilitatory A_2A receptors (A_2AR), the latter selectively engaged at high frequency stimulation associated with synaptic plasticity processes in the hippocampus. A_2AR are activated by adenosine originated from extracellular ATP through ecto-5'-nucleotidase or CD73-mediated catabolism. Using hippocampal synaptosomes, we now investigated how adenosine receptors modulate the synaptic release of ATP. The A_2AR agonist CGS21680 (10-100 nM) enhanced the K⁺-evoked release of ATP, whereas both SCH58261 and the CD73 inhibitor α,β-methylene ADP (100 μM) decreased ATP release; all these effects were abolished in forebrain A_2AR knockout mice. The A₁R agonist CPA (10-100 nM) inhibited ATP release, whereas the A₁R antagonist DPCPX (100 nM) was devoid of effects. The presence of SCH58261 potentiated CPA-mediated ATP release and uncovered a facilitatory effect of DPCPX. Overall, these findings indicate that ATP release is predominantly controlled by A_2AR, which are involved in an apparent feedback loop of A_2AR-mediated increased ATP release together with dampening of A₁R-mediated inhibition. This study is a tribute to María Teresa Miras-Portugal.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"247-255"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9574657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Regulation of TrkB receptor translocation to lipid rafts by adenosine A_2A receptors and its functional implications for BDNF-induced regulation of synaptic plasticity.","authors":"Natália Assaife-Lopes, Vasco C Sousa, Daniela B Pereira, Joaquim A Ribeiro, Ana M Sebastião","doi":"10.1007/s11302-024-10011-4","DOIUrl":"10.1007/s11302-024-10011-4","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"313"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ENTPD1 (CD39) and NT5E (CD73) expression in human glioblastoma: an in silico analysis.","authors":"Elizandra Braganhol, Guilherme Pamplona Bueno de Andrade, Guilherme Tomasi Santos, Marco Antônio Stefani","doi":"10.1007/s11302-023-09951-0","DOIUrl":"10.1007/s11302-023-09951-0","url":null,"abstract":"<p><p>Glioblastoma (GB) is the most common primary brain tumor in adults and carries a dismal prognosis, despite the best available treatment. The 2021 WHO Classification of CNS tumors incorporated molecular profiling to better define the characteristics and prognosis of tumor types and subtypes. These recent advances in diagnosis have not yet resulted in breakthrough therapies capable of shifting the treatment paradigm. NT5E/CD73 is a cell surface enzyme that participates in a complex purinergic pathway in synergy with ENTPD1/CD39 producing extracellular adenosine (ADO) from ATP. ADO promotes tumor progression by inducing immunosuppression, stimulating adhesion, invasion, and angiogenesis. In this study, we performed an in silico analysis of 156 human glioblastoma samples in an unexplored public database to investigate the transcriptional levels of NT5E and ENTPD1. The analysis revealed a significant increase in transcription levels of the genes under study in GB samples versus non-tumor brain tissue samples, in concordance with previous studies. High transcriptional levels of NT5E or ENTPD1 were independently related to a decrease in overall survival (p = 5.4e-04; 1.1e-05), irrespective of the IDH mutation status. NT5E transcriptional levels were significantly higher in GB IDH wild-type patients compared to GB IDH-mutant; however, ENTPD1 levels showed no significant difference, p ≤ 0.001. This in silico study indicates the need for a deeper understanding of the purinergic pathway relation to GB development, also inspiring future population studies that could explore ENTPD1 and NT5E not only as prognostic markers but also as potential therapeutic targets.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"285-289"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9750091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: A₁R-A_2AR heteromers coupled to G_s and G_i/0 proteins modulate GABA transport into astrocytes.","authors":"Sofia Cristóvão-Ferreira, Gemma Navarro, Marc Brugarolas, Kamil Pérez-Capote, Sandra H Vaz, Giorgia Fattorini, Fiorenzo Conti, Carmen Lluis, Joaquim A Ribeiro, Peter J McCormick, Vicent Casadó, Rafael Franco, Ana M Sebastião","doi":"10.1007/s11302-024-10012-3","DOIUrl":"10.1007/s11302-024-10012-3","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"315-316"},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}